Penicillin-derived inhibitors that simultaneously target both metallo- and serine-beta-lactamases

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1299-304. doi: 10.1016/j.bmcl.2003.12.037.

Abstract

The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described. These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes. Selected (mercaptomethyl)penicillinates are shown to inactivate both metallo- and serine-beta-lactamases and to display synergism with piperacillin against beta-lactamase producing strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Delivery Systems / methods*
  • Humans
  • Membrane Proteins / antagonists & inhibitors*
  • Penicillins / chemistry*
  • Penicillins / pharmacology
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Ribosomal Proteins / antagonists & inhibitors*
  • Serine*
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / metabolism

Substances

  • Membrane Proteins
  • Penicillins
  • Protease Inhibitors
  • Ribosomal Proteins
  • beta-Lactamase Inhibitors
  • Serine
  • beta-Lactamases